Adding LAM-001 inhaled therapy leads to broad benefits for PH
Treatment increased exercise capacity, reduced symptom severity: Early data
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An experimental inhaled therapy called LAM-001 significantly reduced symptom severity for all patients who completed a small Phase 2a clinical trial for pulmonary hypertension with interstitial lung disease (PH-ILD) and pulmonary arterial hypertension.
“These findings are encouraging for patients and the broader pulmonary hypertension community and support continued development of LAM-001 in PH-ILD, where meaningful therapeutic advances remain urgently needed,” Aaron B. Waxman, MD, PhD, said in a press release from Orphai Therapeutics, the developer of LAM-001. Waxman is the director of the Pulmonary Vascular Disease Program at Brigham and Women’s Hospital.
The data comes alongside an announcement that Quince Therapeutics has acquired Orphai and LAM-001. Quince will continue developing the medication and expects to launch a Phase 2b clinical trial for PH-ILD later this year. Data from the Phase 2b study is expected in early 2028.
The challenges of vascular remodeling in PH-ILD
Pulmonary hypertension (PH) is a group of disorders characterized by high blood pressure in the vessels that supply the lungs. A key feature is pulmonary vascular remodeling, a process by which these vessels change their structure in response to the ongoing stress of high blood pressure.
Several factors and underlying conditions can cause the rise in blood pressure seen in PH. In PH-ILD, it is related to scarring and inflammation in lung tissue, which progresses alongside vascular remodeling. Although treatment options are approved for PH-ILD, symptoms can remain challenging for many individuals with the condition.
“Patients with PH-ILD continue to face substantial limitations in daily functioning and a high risk of clinical deterioration despite currently available therapies,” Waxman said.
LAM-001 is being tested as an add-on therapy to help people with PH whose symptoms didn’t resolve with standard treatments. It is an inhaled formulation of sirolimus (also known as rapamycin), an inhibitor of the mTOR signaling pathway.
mTOR may contribute to the cell growth that drives vascular remodeling in PH. Researchers expect that by reducing mTOR activity, LAM-001 may reduce remodeling and boost heart and lung function. The medication may also have anti-scarring activity.
The Phase 2a study (NCT05798923) tested LAM-001 in 10 people with PH-ILD or pulmonary arterial hypertension (PAH), a form of PH caused by the narrowing of lung blood vessels. Participants with either condition inhaled the therapy daily for 24 weeks (about six months) in addition to standard treatments. After this, they had the option to continue receiving the therapy for up to one year.
All participants started the study in World Health Organization (WHO) functional class III, meaning their PH symptoms weren’t present at rest but limited their everyday activities.
Three PAH participants and one PH-ILD participant dropped out of the study early for reasons unrelated to LAM-001. The six participants who completed the main treatment period all improved to WHO functional class II, indicating a reduction in symptom severity. Across all participants and the maximum one year of treatment, two also reached WHO functional class I, meaning they didn’t experience symptoms during everyday activities.
The trial’s main goal was to measure change in peak oxygen uptake, the maximum volume of oxygen that the body can use during exercise. Higher peak oxygen uptake corresponds with higher exercise capacity. Across the six participants, the mean increase in this metric was 5.4%. The four participants with PH-ILD experienced a 6.7% increase.
Consistency across multiple lung health markers
Other measurements of lung health also showed improvements. The six-minute walk distance (6MWD), or how far participants could walk in six minutes, a standard metric of exercise capacity, increased by an average of 81.3 meters (266.7 feet) in the overall group and 67.4 meters (221.1 feet) in the PH-ILD subgroup. Pulmonary vascular resistance (PVR), a measure of how difficult it is for blood to move from the heart to the lungs, decreased at rest and during exercise.
Additionally, participants saw decreases in biological markers of heart disease and increases in their forced vital capacity, which is the amount of air a person can exhale after a deep breath.
“What is particularly notable in these early data is the consistency of improvement observed across several important markers of disease burden, including exercise capacity, pulmonary vascular resistance, cardiac stress biomarkers and lung function,” Waxman said. “Improvements in measures such as 6MWD and PVR are especially encouraging given their clinical relevance in pulmonary hypertension and may suggest broader effects on cardiopulmonary physiology.”
Participants generally tolerated LAM-001 well, with no serious safety events related to the medication. Three mild drug-related events occurred: cough, cough with mucus (productive cough), and gum disease.
These findings support the continued development of LAM-001 for PH, particularly PH-ILD, according to Quince. Based on the results, the company is planning a Phase 2b trial focused on this population. Another planned Phase 2 clinical trial will include participants with PH associated with sarcoidosis.
